title: Evaluation of the cyto/genotoxicity profile of oxime K048 using human peripheral blood lymphocytes: an introductory study.
abstract: This study investigates the effects of oxime K048 (730, 200, and 7.3nM) on the viability and chromosome stability of human peripheral blood lymphocytes (PBLs) after a 30min exposure in vitro. Cytotoxicity was tested by a viability assay with ethidium bromide and acridine orange. For the evaluation of the genotoxic potential, we used comet assays, cytokinesis-blocked micronucleus (CBMN) assay, and chromosome aberration (CA) analysis. We found acceptable cytotoxicity for K048 (9.7±2.1% non-viable PBL at highest concentration vs. 7.3±2.5% in control; apoptosis dominated over necrosis). Overall primary DNA damage was low and not significantly different from controls. The hOGG1-comet assay showed a slight increase in the level of oxidative DNA damage. In oxime treated PBLs, we found 13-19 MN compared to 15 MN in control cultures. The frequencies and types of CA in oxime-treated PBLs did not significantly differ from controls. K048 showed acceptable biocompatibility at the level of cell viability and chromatin/chromosome integrity. Since no increase in secondary genome damage was detected, the primary DNA lesions may have resulted from treatment-induced cell stress, subsequently becoming repaired and not fixed as chromosome aberrations. The toxicity profile of K048 should be further studied and compared with other clinically relevant oximes.
authors.affiliation: Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10001 Zagreb, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Lucić Vrdoljak
authors.forename: Suzana
authors.initials: S
authors.lastname: Žunec
authors.forename: Božica
authors.initials: B
authors.lastname: Radić
authors.forename: Radovan
authors.initials: R
authors.lastname: Fuchs
authors.forename: Davor
authors.initials: D
authors.lastname: Želježić
authors.forename: Nevenka
authors.initials: N
authors.lastname: Kopjar
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002869:Chromosome Aberrations / Q000187:drug effects; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015162:Micronucleus Tests / Q000379:methods; D010091:Oximes / Q000008:administration & dosage / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: C488676:1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane; D010091:Oximes; D011726:Pyridinium Compounds
keywords: Chromosome aberrations; DNA damage; In vitro; Lymphocyte; Micronuclei; Oxime